ually is not necessary when dosing instructions are followed. In controlled trials in heart failure patients, the incidence of hypotension in valsartan-treated patients was 5.5% compared to 1.8% in placebo-treated patients. In the Valsartan in Acute Myocardial Infarction Trial (VALIANT), hypotension in post-myocardial infarction patients led to permanent discontinuation of therapy in 1.4% of valsartan-treated patients and 0.8% of captopril-treated patients.
Since the vasodilation induced by amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration. Do not initiate treatment with Exforge HCT in patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.
If excessive hypotension occurs with Exforge HCT, the patient should be placed in a supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
5.3 Increased Angina and/or Myocardial Infarction
Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration or severity of angina or acute myocardial infarction upon starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated.
5.4 Impaired Hepatic Function
Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function.
As the majority of valsartan is eliminated in the bile, patients with mild-to-moderate hepatic impairment, including patients with biliary obstructive disorders, showed lower valsartan clearance (higher AUCs).
In patients with impaired hepatic function or progressive liver disease, minor alterations of fluid and electrolyte balance, such as those resulting from diuretic use, may precipitate hepatic coma.
Therefore, avoid the use of Exforge HCT in patients with severe hepatic impairment. When administering Exforge HCT to patients with mild-to-moderate hepatic impairment, including patients with biliary obstructive disorders, monitor for worsening of hepatic or renal function, including fluid status and electrolytes, and adverse reactions.
5.5 Impaired Renal FunctionAs a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar outcomes have been reported with valsartan.
In studies of ACE inhibitors in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported. In a 4-day trial of valsartan in 12 hypertensive patients with unilateral renal artery stenosis, no significant increases in serum creatinine or blood urea nitrogen were observed. There has been no long-term use of valsartan in patients with unilateral or bilateral renal artery stenosis, but an effect similar to t
